The article presents an outline of the life and scientific contribution of Victor Almon McKusick (1921–2008), an outstanding medical geneticist, professor at Johns Hopkins University, and honorary member of the Russian Academy of Sciences. The scientist's life path is traced from his childhood to his long-term work at Johns Hopkins University, where he progressed from a cardiologist to the founder of an independent Department of Medical Genetics (1957). Four key achievements are highlighted that justify recognizing McKusick as the "father of genetic medicine": the establishment of medical genetics as an independent clinical discipline with a system of education and international courses; pioneering work in human gene mapping; leadership in the Human Genome Project and the creation of the HUGO organization; and the development of the catalog of Mendelian inheritance in humans (MIM/OMIM). The author's personal recollections of a training course in Bar Harbor (1989) and medical genetic counseling at the William Osler Hospital are presented, along with information on how the experience of organizing genetic care in the USA influenced the opening of the first Genetic Clinic in Russia, in Tomsk (1994).

The article traces Victor McKusick's connections with Russian genetics, from the publication of the Russian translation of his book Human Genetics (1967) to his three visits to the USSR (in 1969, 1978, and 1989). It covers McKusick's presentation at the 14th International Genetics Congress in Moscow (1978), where he substantiated the importance of clinical genetics for human genetics as a whole and highlighted the contributions of Soviet scientists (Timofeev–Resovsky, Dubinin) to the development of key concepts. His participation in the Consultative Meetings of HUGO, UNESCO, and the State Committee for Science and Technology (GKNT) in Moscow (1989) is described, as well as the translation of the catalog Human Hereditary Traits by staff of the Institute of Medical Genetics of the USSR Academy of Medical Sciences. Special attention is given to the problem of phenotypic analysis in the genetic clinic and its connection with the Russian tradition of phenogenetics. In conclusion, V. McKusick is characterized as a historian of medical genetics; three key points from his lecture in Bar Harbor (1989) are highlighted: Mendelism as the conceptual basis of nosology; the unity of medical genetics and human genetics; and the significance of somatic mutations for the future of medical genetics.

The article examines the structure of eponymous names of hereditary diseases, syndromes, and traits catalogued in the OMIM (Online Mendelian Inheritance in Man) database, created by Victor McKusick. It is shown that among more than 30,000 entries in the catalogue, 347 names (1.7%) are eponyms recommended as the primary designation. Four categories of eponyms have been identified and characterised: anthroponyms (82.4%), acronyms (14.7%), toponyms (2.3%), and ethnonyms (0.6%). Examples of each category are provided. The problem of pejorative names for hereditary syndromes is considered separately, along with the ethical aspects of using such terms when communicating with patients and the didactic value of figurative names in teaching clinical genetics. The cultural and historical significance of eponymic terminology is discussed as a means of preserving the memory of outstanding researchers and events.

This article analyzes the nature of genetic heterogeneity in human hereditary diseases. It suggests that genetic heterogeneity allows for the identification of key genes for numerous human phenotypic traits and, perhaps, on this basis, the creation of a unique level of genotype-phenotype relationships. The problem of shared transcriptional events for genes forming a single functional group in the OMIM phenotypic series is considered.

This article analyzes allelic genetic heterogeneity of human hereditary diseases. This type of genetic heterogeneity allows to elucidate the architecture of a genetic locus, demonstrate that different gene exons encode regions of varying significance, identify gene regulatory domains (tissue-specific enhancers), and reveal the critical role of introns in alternative splicing, as well as "hot spots" in gene structure and a number of other features of gene structure and function.

Background. DNA extracted from FFPE specimens not always suitable for use in genetic research. Due to that reason, quality control is crucial during all steps of sample preparation for NGS sequencing. In this work we determined preanalytical and postanalytical predictors of successful sequencing of targeted libraries prepared using TSO 500 HT assay. Aim: to suggest quality control metrics and thresholds for each of the parameter based on the analysis of 293 targeted libraries prepared using TSO 500 HT assay for tumor DNA samples extracted from FFPE blocks. To develop recommendations for successful library preparation and sequencing. Methods. For 268 cases of various types of cancer, a pathomorphological study was performed, followed by DNA isolation, and 293 targeted libraries were prepared using the TruSight Oncology 500 High Throughput protocol (Illumina, USA). The libraries then were sequenced on the NovaSeq 6000 and NextSeq 2000 according to the NovaSeq 6000 and NextSeq 1000/2000 System Guides. Results. Including a stage of additional purification and concentration of extracted DNA in the sample preparation protocol increases the probability of successful sequencing by 34%. This modification also significantly increases bioinformatic key metrics: median exon coverage, median insert size, and percentage of exons sequenced with coverage >50x. The average library length and library concentration were identified as significant predictors of the success of sequencing performance. The probability of success increases when sequencing libraries with a concentration of at least 15 ng/μl and an average length of at least 240 bp.

Introduction. The introduction of massively parallel sequencing (MPS) technologies in clinical practice requires the development of cost-effective and reproducible sample preparation protocols. Particular interest is in the use of Tn5 transposase for tagmentation, which allows for the combination of DNA fragmentation and adapter ligation in a single reaction, reducing the time and number of steps compared to standard ultrasonic fragmentation methods. Aim: to develop a protocol for preparing DNA libraries using domestically produced Tn5 Transposase, followed by hybridization enrichment for targeted sequencing. Methods. The study was performed on genomic DNA isolated from human peripheral blood leukocytes. Pre-libraries were generated by tagmentation using the SyntEra-DNA kit based on Tn5 transposase. Enrichment of target regions of the EGFR gene was achieved by two-round hybridization with a specially selected pool of biotinylated probes, followed by capture on streptavidin magnetic particles. Sequencing of the enriched libraries was performed on the Illumina MiSeq platform. Sequencing metrics from previously obtained DNA libraries prepared using the commercial SureSelectXT kit were used as a reference sequencing metrics. Results. The developed protocol enabled the generation of a DNA library with an average fragment length of approximately 300 bp and a concentration sufficient for sequencing. The proportion of base mapped to EGFR target regions with coverage of at least 10× was 98%, and the proportion with coverage of at least 20× was 96%. The proportion of bases mapped to EGFR target regions was 87%. The Fold-80 base penalty was 1.5, indicating uniform coverage across the target region. Conclusions. The proposed protocol, based on Tn5 transposase and domestic reagents, allowed us to create a DNA library that is suitable for targeted MPS analysis and confirms the fundamental applicability of the developed approach for the effective enrichment of target regions.

Background. The implementation of artificial intelligence (AI) algorithms in the diagnosis of inherited diseases opens new prospects for personalized medicine. However, determining the required sample size remains a critical limitation hindering the clinical validation of such systems. For orphan diseases, collecting representative data is associated with objective difficulties, especially in the context of ethnically heterogeneous mutational landscapes. Objective. To present a methodological analysis of modern approaches to determining sample size for the validation of AI-based prognostic and diagnostic algorithms in the context of inherited diseases, using Duchenne muscular dystrophy (DMD) as a model pathology. Methods. A narrative review of literature covering the period 2015–2025 was conducted, covering the epidemiology of DMD, methods for calculating sample size in AI-based studies, Bayesian approaches, transfer learning, and innovative statistical frameworks. An imputed sample size calculation is presented to illustrate the complexities of epidemiological studies of rare diseases. Results. Traditional power calculation methods, which require hundreds of observations, are often inapplicable given the population incidence of DMD of 1:3500–5000 and the need for stratification by ethnic group. An imputed calculation to detect differences between groups with frequencies of 2.5 and 4.0 per 10,000 males demonstrates that a total sample size of over 529,000 observations is required, creating significant limitations for traditional designs. Innovative approaches are analyzed: Bayesian hierarchical models, transfer learning, and specialized sample planning tools (planningML). Conclusion. The transition from empirical rules to rigorous mathematical sample planning methods is a prerequisite for the clinical validity and ethical implementation of AI-based diagnostics for hereditary diseases. Bayesian methods and transfer learning can be considered promising tools for working with limited data; however, they do not replace the requirements for independent validation and adequate uncertainty assessment. Early engagement with regulatory authorities and transparent reporting in accordance with the extended versions of TRIPOD for AI are recommended.

In 2024, the latest version of the International System for Human Cytogenome Nomenclature (ISCN) was published, and it remains the current version. This version represents one of the most significant revisions of the ISCN in order to develop a more user-friendly manual. New chapters have been introduced on general ISCN rules and genomic mapping nomenclature, examples and descriptions of chromosomal abnormality and mosaicism findings have been added, and additional abbreviations have been introduced. A key aspect of ISCN 2024 is the creation of a standardized nomenclature for the consistent description of research results, regardless of the cytogenomic technology used. The review presents the most significant changes made to individual chapters regarding the general provisions of constitutional cytogenomics, classical cytogenetic research, and in situ hybridization.

The International System for Human Cytogenomic Nomenclature (ISCN) is the current guideline defining nomenclature standards for reporting the results of cytogenomic studies, including chromosomal microarray analysis. The 2024 edition updates the rules for reporting chromosomal abnormalities detected using cytogenomic methods, thereby ensuring uniformity in the recording and interpretation of test results. This review presents the most significant changes to the nomenclature for chromosomal microarray analysis.

KBG syndrome is an autosomal dominant disorder characterized by delays in psychomotor and speech development, cognitive and behavioral impairments, and distinctive phenotypic features. This paper presents two clinical cases of KBG syndrome with pathogenic heterozygous variants in the ANKRD11 gene. Both patients exhibited minor congenital anomalies (dolichocephaly, elongated face, synophrys, long eyelashes, broad nasal bridge, wide mouth, single transverse palmar creases, shortening and clinodactyly of the fifth fingers of both hands), disproportionate body, delayed psychomotor and speech development, EEG abnormalities, and ventriculomegaly. However, a hallmark feature of KBG syndrome macrodontia was absent in both patients. In one patient the condition was accompanied by epilepsy and autism-like behavioral features, whereas the other showed delayed closure of the anterior fontanelle and conductive hearing loss. The marked phenotypic variability of KBG syndrome underscores the key role of next-generation sequencing in the diagnosis of this disorder.